The liver is a vital organ in various vertebrates and some other animals. In the human body, the liver is the largest internal organ, providing many essential functions, including metabolic, exocrine and endocrine functions. The liver is necessary for survival as without liver function a human can only survive up to 24 hours. Disorders of the liver, including liver failure and end-stage liver diseases, are responsible for a large number of deaths around the world and are a major burden on the health care system. Based on the organ procurement and transplantation network (OPTN), transplantation of whole liver from cadaveric donors was shown to be effective in saving the lives of about 7,000 patients who receive such livers annually in the U.S. However, about 16,000 patients remain untreated on the waiting list annually. This shortage of suitable livers leads to about 4,000 deaths in the US alone.
A common reason of liver donor ineligibility is excessive fat content, known as macrosteatosis, which is characterized by the presence of large lipid droplets inside the parenchymal cells of the liver, hepatocytes. Furthermore, these droplets displace the nuclei to the cell periphery. Methods to recover such livers could enhance donor availability. One such method that has been proposed is to subject these livers to machine perfusion in the presence of compounds that promote accelerated lipid droplet breakdown and metabolism. However, a thorough exploration of such compounds, and combinations thereof, is necessary to achieve “de-fatting” of the livers in a timescale of a few hours.
Thus, there is a need for systems and methods for identifying compounds or agents for de-fatting and functional recovery of macrosteatotic hepatocytes.